cAMP signaling can antagonize potent glucocorticoid post-transcriptional inhibition of stanniocalcin gene expression.

Stanniocalcin (STC) is a glycoprotein hormone first discovered in fish as a homeostatic regulator of calcium and phosphate transport; it has recently been discovered in mammals, in which it appears to have a similar role. It has also been implicated in a number of different physiological processes through correlative studies, but the factors regulating its production have not been elucidated. In this report, we show that steady-state STC mRNA levels in the mouse corticotrope tumor line, AtT-20, were exquisitely sensitive to glucocorticoids. Hydrocortisone and dexamethasone (Dex) induced a dramatic reduction in steady-state STC mRNA levels in AtT-20 cells through a post-transcriptional mechanism. Similarly, glucocorticoids down-regulated STC mRNA levels in the human fibrosarcoma cell line, HT1080. The specificity of the glucocorticoid-mediated decrease in STC mRNA abundance was shown using the glucocorticoid receptor antagonist, RU-486. Activation of the cAMP-signaling pathway in glucocorticoid-cultured AtT-20 cells transiently restored STC gene expression. Treatment of AtT-20 cells with the transcriptional inhibitor, actinomycin D, rescued steady-state STC mRNA levels from Dex-induced repression, indicating that the Dex-mediated decrease in STC gene expression requires current gene transcription. Taken together, these results describe a unique model system in which cAMP-stimulated events can reverse post-transcriptional repression of gene expression by glucocorticoids.

Effect of selection of swine for high and low immune responsiveness on monocyte superoxide anion production and class II MHC antigen expression.

Monocyte function was investigated in second (G2) and third (G3) generation pigs selected for high and low antibody and cell-mediated immune responsiveness. In groups of pigs from the high-and low-immune response lines, monocyte release of superoxide anion (O2-) was assayed in response to phorbol 12-myristate-13-acetate and expression of the Class II-MHC (MHC-II) antigens SLA-DR and SLA-DQ, determined using flow cytometry. Analysis of variance using a linear model demonstrated no significant intergroup differences in O2- production by lymphokine-activated monocytes from G2 pigs. In G3 pigs, there were no significant intergroup differences in the percentage of MHC-II+ cells or in the density of expression of either SLA-DR or SLA-DQ. In individual pigs, monocyte SLA-DR and SLA-DQ expression was similar in terms of the percentage of MHC-II+ cells and in the magnitude of MHC-II expression. Litter contributed significantly to variation in monocyte O2- production in G2 pigs (P < or = 0.005) and SLA-DQ (P < or = 0.01) expression. Although the lines differed significantly in correlates of antibody and cell-mediated immune response, there was no apparent effect of selection for high and low immune responsiveness in swine on monocyte O2- production and MHC-II expression.